Autoimmunity is often associated with infectious agents. However, little is known about how the autoimmunity is induced by pathogen. Our long term objective is to understand the events that lead to the breakdown of self-tolerance in the infected individuals. Trypanosoma cruzi infection of the mouse is an excellent model system for this class of diseases. In this case it has been argued that autoimmunity results from the presence of cross-reactive antigens on the parasite and the mammalian host as well as a deregulation of the infected host's immune system. We have isolated five independent monoclonal antibodies that recognize epitopes common to T. cruzi and to the mammalian nervous system. Two of these recognize specific families of lipids and glycolipids some of which we have identified. Monoclonal MAB VESP 6.2 recognizes sulfatides as well as an as yet unidentified minor family of sulfate and phosphate containing lipids. MAB VESP 8.2 recognizes only lipids containing -hydroxy fatty acids and galactose which are only present in myelin. Another monoclonal, MAB DION 10.1.b recognizes a component of coated vesicles of muscle and nerve cells and has the property that it kills mice. A newly characterized trypanosome antigen of the trypomastigote flagellar membrane, F1-1 60, cross reacts with nerve processes. We wish to study the T. cruzi infected mouse system and humans in relation to the antigens that our monoclonal and polyclonal antibodies define. We will fully characterize the common antigens, examine sera of infected people for the antigens they detect and correlate this with the observed pathology. We will especially study the nature of the epitope recognized by MAB DION 10.1.b since this antibody is pathogenic.